Hemodynamic parameters such as heart rate, arterial blood pressure stroke volume fluctuate on a beat-to-beat basis as a result of the dynamic interplay between ongoing perturbations to the cardiovascular system and the response of the regulatory systems. Mathematical analysis of beat-to-beat variability has been shown previously to provide a noninvasive means of assessing the integrity of the closed loop regulation of the cardiovascular system. For example, spectral analysis of heart rate variability has been shown to provide a noninvasive measure of parasympathetic and beta-sympathetic activity. In this proposal we plan to study spontaneous beat-to-beat variability in hemodynamic parameters in response to broad-band perturbations applied to respiratory activity, heart rate and arterial blood pressure. These studies will be conducted in the dog and in man to define the regulatory mechanisms governing beat-to-beat variability in hemodynamic parameters. Abnormalities in hemodynamic parameter variability will be identified in pathophysiological conditions affecting cardiovascular regulation such as heart failure and hypertension. A computer model of beat-to-beat cardiovascular regulation will be developed to elucidate mechanisms of variability in hemodynamic parameters and synthesize the results of the experimental studies. Finally, new clinical diagnostic methods will be developed to identify regulatory dysfunction in a sensitive and quantitative manner.